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Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others. [ABSTRACT FROM AUTHOR]

Abstract Background Trinitrobenzenesulphonic acid (TNBS) induced rat colitis is one of the most widely used models of inflammatory bowel disease (IBD), a condition whose aetiology and pathophysiology are incompletely understood. We have characterized this model at the genomic level using a longitudinal approach. Six control rats were compared with colitic animals at 2, 5, 7 and 14 days after TNBS administration (n = 3). The Affymetrix Rat Expression Array 230 2.0 system was used. Results TNBS-induced colitis had a profound impact on the gene expression profile, which was maximal 5 and 7 days post-induction. Most genes were affected at more than one time point. They were related to a number of biological functions, not only inflammation/immunity but also transport, metabolism, signal transduction, tissue remodeling and angiogenesis. Gene changes generally correlated with the severity of colitis. The results were successfully validated in a subset of genes by real-time PCR. Conclusion The TNBS model of rat colitis has been described in detail at the transcriptome level. The changes observed correlate with pathophysiological disturbances such as tissue remodelling and alterations in ion transport, which are characteristic of both this model and IBD.

Postpartum depression affects a huge number of women and has detrimental consequences. Knowing the factors associated with postpartum depression during pregnancy can help its prevention. Although there is evidence surrounding behavioral or psychological predictors of postpartum depression, there is a lack of evidence of biological forecasters. The aim of this study was to analyze the sociodemographic, obstetric, and psychological variables along with hair cortisol levels during the first, second, and third trimesters of pregnancy that could predict postpartum depression symptoms. A sample of 44 pregnant women was assessed during 3 trimesters of pregnancy and the postpartum period using psychological questionnaires and hair cortisol levels. Participants were divided into 2 groups: a group with postpartum depression symptoms and a group with no postpartum depression symptoms. Results showed significant positive differences between groups in the first trimester regarding the Somatization subscale of the SCL-90-R (p < .05). In the second trimester, significant differences were found in the Somatization, Depression, Anxiety, and GSI subscales (p < .05). In the third trimester significant differences between both groups were found regarding pregnancy-specific stress. We found significant positive differences between groups regarding hair cortisol levels in the first and the third trimester. Hair cortisol levels could predict 21.7% of the variance of postpartum depression symptoms. In conclusion, our study provided evidence that psychopathological symptoms, pregnancy-specific stress, and hair cortisol levels can predict postpartum depression symptoms at different time-points during pregnancy. These findings can be applied in future studies and improve maternal care in clinical settings.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipatic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

Background & Aims: Dietary fiber has been proven to be beneficial in maintaining remission in human ulcerative colitis, an effect related with an increased luminal production of short-chain fatty acids (SCFA). The aim of the present study was to further investigate the mechanisms involved in the intestinal anti-inflammatory effects of dietary fiber in an experimental model of rat colitis., Methods: HLA-B27 transgenic rats (8-10 weeks old) were fed a fiber-supplemented diet (5% Plantago ovata seeds) for 13 weeks before evaluation of the colonic inflammatory status, both histologically and biochemically. The luminal colonic production of SCFA was quantified. In vitro studies were also performed to test the interaction between two SCFA (butyrate and propionate) as inhibitors of cytokine production in THP-1 cells., Results: Dietary fiber supplementation ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture. This effect was associated with a decrease in some of the pro-inflammatory mediators involved in the inflammatory process: nitric oxide, leukotriene B(4), tumor necrosis factor alpha (TNFalpha). The intestinal contents from fiber-treated colitic rats showed a significant higher production of SCFA, butyrate and propionate, than non-treated colitic animals. In vitro studies revealed a synergistic inhibitory effect of butyrate and propionate on TNFalpha production., Conclusions: Dietary fiber supplementation ameliorated colonic damage in HLA-B27 transgenic rats. This effects was associated with an increased production of SCFA, which can act synergistically in inhibiting the production of pro-inflammatory mediators.

The turnover of intestinal epithelial cells is a finely regulated process extending from undifferentiated crypt stem cells to terminally differentiated villus cells. The final phase of this maturation process is apoptosis and extrusion. Recent studies have shown that programmed cell death (PCD) occurs not only in senescent cells and in rapidly developing tissues but also in response to cellular stress preventing damaged cells from entering uncontrolled proliferation without repair. This study examined the role of exogenous nucleotides on cell proliferation, differentiation and apoptosis in organ cultures of human fetal small intestine. The addition of adenosine monophosphate (AMP), a putative stress reactant, to the culture media resulted in the suppression of crypt cell proliferation followed by the restoration of differentiation and the induction of apoptosis across a broad range of villus epithelium when compared with controls without added nucleotide. In contrast, the addition to cytidine monophosphate (CMP) to the culture media did not increase apoptosis, despite the nucleotide being taken up by the fetal small intestine in a similar dose- and time-dependent manner to AMP. Furthermore, Bax mRNA, an apoptosis-inducer gene, was increased with addition of AMP, suggesting that the induction of apoptosis may be channeled through the p53 pathway. These results suggest that a specific exogenous nucleotide, AMP, may have an important role in controlling the dynamic balance of cellular turnover in the developing human small intestine.

The aim of this study was to evaluate the effect of the molecular form of dietary protein (native or enzymatically hydrolyzed) on the total serum protein concentrations and the serum amino acid profile of growing rats at weaning. Wistar male rats at weaning were randomly assigned to one of the four isocaloric and isonitrogenous (12% protein equivalent content) diets and fed for 7 days. The protein sources of the diets were: whey protein, casein and their respective hydrolysates. Differences in the serum amino acid profiles exclusively related to the amino acid composition of the protein (casein or whey proteins) were observed, but differences due to their molecular form were not observed. It is concluded that the use of enzymatic hydrolysates of whey proteins and casein has the same effects as their native proteins on nitrogen intake, body weight gain and serum amino acid profile of growing rats at weaning.